Proteasome inhibitor-based pharmacological and clinical application of.doc

 PAGE \* MERGEFORMAT 14 Proteasome inhibitor-based pharmacological and clinical application of [Keywords:] proteasome inhibitor; cancer; treatment [Abstract] proteasome inhibitors are a class through the ubiquitination pathway blocked by a new class of anticancer drugs, for cancer treatment has good application prospects. Proteasome is widely distributed in eukaryotic cytoplasm and nucleus, with a variety of functions protease complex, while the ubiquitin - proteasome system is the creatures selective degradation of proteins is one important way, these proteins, including transcription factors, tumor inhibitory protein, proto-oncogene, etc.. In vitro and animal model experiments have shown that proteasome inhibitors have a broad anti-tumor effect, the early clinical trials for the clinical application of proteasome inhibitor and further provide a basis for. [Keywords:] proteasome inhibitor; cancer; treatment Ubiquitin - proteasome pathway (ubiquitin proteasome pathway, UPP) is the cytoplasm and the nucleus is different from the lysosomal pathway ATP dependent protein degradation pathway, more than 80% of the cell proteins, including a variety of proteins regulating cell cycle, the degradation of both this way to be completed. Change in its composition will cause the degradation of abnormal proteins, leading to cell dysfunction. Therefore, the proteasome could be a target for cancer treatment, their inhibitors represent a new class of molecular targeted anticancer drugs. 1 Structure and Function of Proteasome 1.1 The structure of proteasome proteasome exists in all eukaryotic cell cytoplasm and nucleus, is highly conserved protease with a variety of catalytic complexes [1]. 26 S proteasome, including a 20 S catalytic units and two units of 19 S regulation, 20 S protease Ticheng barrel shape, from the inner ring and the outer 2 β 2 α rings, each ring contains a 7 subunit. α -subunit to promote the shift into the central pore of substrate hydrolysis center